Biological substance detection chip, biological substance detection device and biological substance detection system

ABSTRACT

There is provided a biological substance detection chip having high detection accuracy. The present technology provides a biological substance detection chip which is composed of a plurality of pixels in which the pixel includes at least a holding surface on which a biological substance is held and a photoelectric conversion unit that is provided below the holding surface and provided on a semiconductor substrate, wherein a partition wall made of a conductor is provided between the pixels on the holding surface. In addition, the present technology provides a biological substance detection device and a biological substance detection system using the biological substance detection chip.

TECHNICAL FIELD

The present technology relates to a biological substance detection chip,a biological substance detection device and a biological substancedetection system.

BACKGROUND ART

In recent years, technical research on gene analysis, protein analysis,cell analysis and the like has progressed in various fields such asmedicine, drug discovery, clinical examination, food, agriculture, andengineering. In particular, recently, the development and practicalapplication of detection technology on chips such as lab-on-a-chip inwhich various reactions such as detection and analysis of biologicalsubstances such as nucleic acids, proteins, cells, and microorganismsare performed in microscale channels and wells provided in the chipshave been progressed. These are being focused on as a method of easilymeasuring biological substances and the like.

For example, PTL 1 discloses an optical detection device including atleast a first substrate in which a plurality of wells are formed, asecond substrate in which a heating unit is provided so that it comes incontact with the wells, a third substrate in which a plurality of lightemitting units are positioned to correspond to the positions of thewells, and a fourth substrate in which a plurality of light detectingunits are positioned to correspond to the positions of the wells. Inthis optical detection device, various reactions that proceed in thewells can be measured.

In addition, for example, PTL 2 discloses a chemical sensor including asubstrate in which an optical detection unit is formed, and a plasmonabsorption layer laminated on the substrate and having a metalnanostructure that causes plasmon absorption. This chemical sensor candetect emission of light caused by binding between a probe materialfixed on the sensor and a target material.

CITATION LIST Patent Literature [PTL 1]

JP 2010-284152A

[PTL 2]

WO 2013/080473

SUMMARY Technical Problem

Even if proteins such as DNA and antibodies, and biological substancessuch as cells are suspended in a sample liquid or fixed, they may shrinkdue to their higher-order structure, which may influence lightdetection.

Therefore, a main object of the present technology is to provide abiological substance detection chip having high detection accuracy.

Solution to Problem

Specifically, first, the present technology provides a biologicalsubstance detection chip which is composed of a plurality of pixels inwhich the pixel at least includes a holding surface on which abiological substance is held and a photoelectric conversion unit that isprovided below the holding surface and provided on a semiconductorsubstrate, wherein a partition wall made of a conductor is providedbetween the pixels on the holding surface.

In the biological substance detection chip according to the presenttechnology, the partition wall can be designed so that a voltage isapplied when the biological substance is detected.

In this case, a positive voltage or a negative voltage can be applied toall of the partition walls, and for the partition walls, a positivevoltage or a negative voltage can be applied to the respective partitionwalls.

In addition, a magnitude of a voltage applied to the partition walls maybe changed for each partition wall.

In the biological substance detection chip according to the presenttechnology, some or all of the partition walls that are able to beconductive on the holding surface may be covered with a protective film.

Regarding the biological substance that can be detected by thebiological substance detection chip according to the present technology,one or more biological substances selected from among nucleic acids,proteins, cells, microorganisms, chromosomes, ribosomes, mitochondria,organelles (cell organelles), and complexes thereof may be exemplified.

Next, the present technology provides a biological substance detectiondevice, including a biological substance detection chip which iscomposed of a plurality of pixels, in which the pixel includes at leasta holding surface on which a biological substance is held and aphotoelectric conversion unit that is provided below the holdingsurface, and in which a partition wall made of a conductor is providedbetween the pixels on the holding surface, and an analysis unit thatanalyzes electrical information acquired by the biological substancedetection chip.

The present technology also provides a biological substance detectionsystem, including a biological substance detection chip which iscomposed of a plurality of pixels, in which the pixel includes at leasta holding surface on which a biological substance is held and aphotoelectric conversion unit that is provided below the holdingsurface, and in which a partition wall made of a conductor is providedbetween the pixels on the holding surface; and an analysis device thatanalyzes electrical information acquired by the biological substancedetection chip.

In the present technology, “biological substance” widely includesnucleic acids, proteins, cells, microorganisms, chromosomes, ribosomes,mitochondria, organelles (cell organelles), complexes thereof, and thelike. Cells include animal cells (such as blood cell lineage cells) andplant cells. Microorganisms include bacteria such as E. coli, virusessuch as tobacco mosaic virus, and fungi such as yeast.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a schematic conceptual view schematically showing interactionsbetween biological substances S that can be detected by a biologicalsubstance detection chip 1, a biological substance detection device 2,and a biological substance detection system 3 according to the presenttechnology.

FIG. 2 is a schematic conceptual view schematically showing interactionsbetween biological substances S that can be detected by the biologicalsubstance detection chip 1, the biological substance detection device 2,and the biological substance detection system 3 according to the presenttechnology.

FIG. 3 is a schematic conceptual view schematically showing interactionsbetween biological substances S that can be detected by the biologicalsubstance detection chip 1, the biological substance detection device 2,and the biological substance detection system 3 according to the presenttechnology.

FIG. 4 is a schematic conceptual view schematically showing screening ofother substances that can be performed by the biological substancedetection chip 1, the biological substance detection device 2, and thebiological substance detection system 3 according to the presenttechnology.

FIG. 5 is a schematic conceptual view schematically showing screening ofother substances that can be performed by the biological substancedetection chip 1, the biological substance detection device 2, and thebiological substance detection system 3 according to the presenttechnology.

FIG. 6 is a schematic conceptual view schematically showing screening ofother substances that can be performed by the biological substancedetection chip 1, the biological substance detection device 2, and thebiological substance detection system 3 according to the presenttechnology.

FIG. 7 is a schematic plan view schematically showing a first embodimentof the biological substance detection chip 1 according to the presenttechnology as viewed from above.

FIG. 8 is a schematic end view taken along the line A-A, schematicallyshowing the first embodiment of the biological substance detection chip1 according to the present technology.

FIG. 9 is a schematic end view schematically showing a modified exampleof the first embodiment of the biological substance detection chip 1according to the present technology.

FIG. 10 is a schematic plan view schematically showing a secondembodiment of the biological substance detection chip 1 according to thepresent technology as viewed from above.

FIG. 11 is a schematic plan view schematically showing a first modifiedexample of the second embodiment of the biological substance detectionchip 1 according to the present technology as viewed from above.

FIG. 12 is a schematic plan view schematically showing a second modifiedexample of the second embodiment of the biological substance detectionchip 1 according to the present technology as viewed from above.

FIG. 13 is a schematic plan view schematically showing a third modifiedexample of the second embodiment of the biological substance detectionchip 1 according to the present technology as viewed from above.

FIG. 14 is a schematic plan view schematically showing a thirdembodiment of the biological substance detection chip 1 according to thepresent technology as viewed from above.

FIG. 15 is a schematic plan view schematically showing a first modifiedexample of the third embodiment of the biological substance detectionchip 1 according to the present technology as viewed from above.

FIG. 16 is a schematic plan view schematically showing a second modifiedexample of the third embodiment of the biological substance detectionchip 1 according to the present technology as viewed from above.

FIG. 17 is a schematic plan view schematically showing a third modifiedexample of the third embodiment of the biological substance detectionchip 1 according to the present technology as viewed from above.

FIG. 18 is a schematic plan view schematically showing a fourthembodiment of the biological substance detection chip 1 according to thepresent technology as viewed from above.

FIG. 19 is a schematic plan view schematically showing a modifiedexample of the fourth embodiment of the biological substance detectionchip 1 according to the present technology as viewed from above.

FIG. 20 is a schematic end view taken along the line B-B, schematicallyshowing the first embodiment of the biological substance detection chip1 according to the present technology.

FIG. 21 is a schematic end view taken along the line C-C, schematicallyshowing the third embodiment of the biological substance detection chip1 according to the present technology.

FIG. 22 is a block diagram showing a concept of the biological substancedetection device 2 according to the present technology.

FIG. 23 is a block diagram showing a concept of the biological substancedetection system 3 according to the present technology.

Description of Embodiments

Hereinafter, preferable embodiments for implementing the presenttechnology will be described with reference to the drawings. Theembodiments described below show examples of representative embodimentsof the present technology, but the scope of the present technologyshould not be narrowly understood based on the embodiments. Here,description will proceed in the following order.

1. Overview of Biological Substance Detection performed by PresentTechnology

(1) Detection of Biological Substance S Itself

(2) Detection of Interactions of Biological Substance S

(3) Screening of Other Substances

2. Biological Substance Detection Chip 1

(1) First Embodiment

(2) Second Embodiment

(3) Third Embodiment

(4) Fourth Embodiment

(5) Other Examples

(6) Method of Applying Voltage

3. Biological Substance Detection Device 2

4. Biological Substance Detection System 3

1. Overview of Biological Substance Detection Performed by PresentTechnology

An overview of detection of a biological substance S performed by abiological substance detection chip 1, a biological substance detectiondevice 2, and a biological substance detection system 3 according to thepresent technology will be described. The biological substance detectionchip 1 and the biological substance detection device 2, and thebiological substance detection system 3 according to the presenttechnology can be used for (1) detection of a biological substance Sitself, (2) detection of interactions of the biological substance S, (3)screening of other substances (for example, medicinal components) usingbiological substance S and the like. Here, each detection is performedon a holding surface 111 of the biological substance detection chip 1 tobe described below.

(1) Detection of Biological Substance S Itself

For example, the present technology can be used for detectingbio-substances such as red blood cells, white blood cells, platelets,cytokines, hormone substances, sugars, lipids, proteins and the likecontained in body fluids such as blood, urine, feces, and saliva;microorganisms such as bacteria, fungi, viruses and the like containedin body fluids and water; and genes in cells and microorganisms. Forexample, after staining with a dye that acts specifically on a detectiontarget substance or a non-detection target substance, the presence of adetection target substance can be detected depending on the presence ofdesired light detection. The detection results can be used for diseasediagnosis, internal environment diagnosis, water quality examination andthe like.

(2) Detection of Interactions of Biological Substance S

For example, the present technology can be used to detect interactionssuch as protein interactions, nucleic acid hybridization, and binding ofcytokines and hormone substances to receptors. Specific detectionexamples will be described with reference to FIGS. 1 to 3 .

For example, as shown in A to D in FIG. 1 , a biological substance 51such as a protein or a receptor (or an imitation of a receptor) is fixedon a holding surface 111 (refer to A in FIG. 1 ), and fixed dyes such asfluorescent dyes F1 to F3 are added to biological substances S2 to S4for checking the interaction thereof (refer to B in FIG. 1 ). Then, thebiological substances S3 and S4 that do not interact with the biologicalsubstance S1 are washed off (refer to C in FIG. 1 ), and the interactionbetween the biological substance S1 and the biological substance S2 canbe detected by detecting the fluorescent dye F1 from the holding surface111 (refer to D in FIG. 1 ).

For example, as shown in E to H in FIG. 1 , the biological substance S1such as a cell is fixed on the holding surface 111, and an entrappedilluminant F1 can be detected via a transporter t (for example, atransporter in a cell membrane) of the biological substance S1.

For example, as shown in A to D in FIG. 2 , a probe S5 composed of DNA,RNA or the like is fixed to the holding surface 111 (refer to A in FIG.2 ), and a sample containing DNA S6 and S7 that can be targets, and anintercalator I are added (refer to B in FIG. 2 ). Then, when the DNA S6having a sequence complementary to the probe S5 is contained in thesample, a hybridization reaction occurs. The DNA S7 that is nothybridized is washed off (refer to C in FIG. 2 ), and hybridizationbetween the probe S5 and the target DNA S6 can be detected by detectinglight from the intercalator I from the holding surface 111 (refer to Din FIG. 2 ).

For example, as shown in A to D in FIG. 3 , a biological substance S8 isfixed on the holding surface 111(refer to A in FIG. 3 ), and abiological substance S9 that interacts with the biological substance S8to form a new substance S10 is added (refer to B in FIG. 3 ). Next, adye such as a fluorescent dye F4 that specifically binds to thesubstance S10 is added (refer to C in FIG. 3 ), and the fluorescent dyeF4 is detected from the holding surface 111 (refer to D in FIG. 3 ), andthus the interaction between the biological substance S8 and thebiological substance S9 can be detected.

(3) Screening of Other Substances

For example, the present technology can be used for screening ofsubstances that can be agonists or antagonists of various receptors, andscreening of agents for inhibiting production of various microorganisms,antibacterial agents, bactericidal agents and the like. Specificdetection examples will be described with reference to FIG. 4 to FIG. 6.

For example, as shown in A to D in FIG. 4 , a receptor R1 (or animitation of the receptor R1) is fixed on the holding surface 111 (referto A in FIG. 4 ), and fixed dyes such as fluorescent dyes F5 to F7 areadded to substances d1 to d3 for checking operability of the receptor R1(refer to B in FIG. 4 ). Then, the substances d2 and d3 that do not bindto the receptor R1 are washed off (refer to C in FIG. 4 ), and it ispossible to perform screening of the substance d1 that can be an agonistof the receptor R1 by detecting the fluorescent dye F5 from the holdingsurface 111 (refer to D in FIG. 3 ).

For example, as shown in A to E in FIG. 5 , a receptor R2 (or animitation of the receptor R2) is fixed on the holding surface 111 (referto A in FIG. 5 ), and a substance d4 for checking antagonism of thereceptor R2 is added (refer to B in FIG. 5 ). Next, a ligand L1 thatbinds to the receptor R2 to which a dye such as a fluorescent dye F8 isfixed is added (refer to C in FIG. 5 ). In this case, if the substanced4 can be an antagonist of the receptor R2, the ligand L1 cannot bind tothe receptor R2 because the receptor R2 and the substance d4 are alreadybound to each other (refer to C in FIG. 5 ). In this state, after theligand L1 that does not bind to the receptor R2 is washed off (refer toD in FIG. 5 ), even if an attempt is made to detect the fluorescent dyeF8 from the holding surface 111, light is not detected because thefluorescent dye F8 is not present on the holding surface 111 due to thewashing (refer to E in FIG. 5 ).

On the other hand, for example, as shown in A to E in FIG. 6 , areceptor R3 (or an imitation of the receptor R3) is fixed on the holdingsurface 111 (refer to A in FIG. 6 ), and a substance d5 for checkingantagonism of the receptor R3 is added (refer to B in FIG. 6 ). Next, aligand L2 that binds to the receptor R3 to which a dye such as afluorescent dye F9 is fixed is added (refer to C in FIG. 6 ). In thiscase, when the substance d5 cannot be an antagonist of the receptor R3,the ligand L2 binds to the receptor R3 (refer to D in FIG. 6 ). In thisstate, when the substance d5 that does not bind to the receptor R3 iswashed off (refer to D in FIG. 6 ), the fluorescent dye F9 is detectedfrom the holding surface 111 (refer to E in FIG. 6 ).

In this manner, as shown in FIG. 5 and FIG. 6 , it is possible toperform screening of the substance d4 that can be an antagonist of thereceptor R3 depending on whether the fluorescent dye F8 or thefluorescent dye F9 is detected from the holding surface 111.

2. Biological Substance Detection Chip 1

The biological substance detection chip 1 according to the presenttechnology is composed of a plurality of pixels 11, and the pixel 11includes at least a holding surface 111 on which a biological substanceS is held and a photoelectric conversion unit 112 that is provided belowthe holding surface 111 and provided on a semiconductor substrate 12.Here, a partition wall 13 made of a conductor is provided between thepixels 11 on the holding surface 111. Hereinafter, description willproceed with reference to embodiments.

Examples of conductors constituting the partition wall 13 include ametal, and regarding the metal, for example, tungsten (W), aluminum(Al), copper (Cu), titanium (Ti) or the like can be used.

(1) FIRST EMBODIMENT

FIG. 7 is a schematic plan view schematically showing a first embodimentof the biological substance detection chip 1 according to the presenttechnology as viewed from above, and FIG. 8 is a schematic end viewtaken along the line A-A, schematically showing the first embodiment ofthe biological substance detection chip 1 according to the presenttechnology. The biological substance detection chip 1 according to thefirst embodiment has an effective pixel region 11E in which a pluralityof pixels 11 are two-dimensionally arranged in a matrix. Each pixel 11includes at least a holding surface 111 on which a biological substanceS is held and a photoelectric conversion unit 112. In the photoelectricconversion unit 112, for example, a photoelectric conversion elementsuch as a photodiode can be freely used. In addition, although notshown, each pixel 11 may include a pixel circuit composed of a chargestorage unit, a plurality of transistors, a capacitive element and thelike. Although not shown, an optical black pixel, a wiring region andthe like can be provided on the outside (invalid pixel region O) of theeffective pixel region 11E.

The holding surface 111 is not particularly limited as long as it has aconfiguration that can hold the biological substance S, and a surfacetreatment can be freely used. For example, the holding surface 111 canbe formed by applying a photosensitive silane coupling agent or the likethat is modified with ultraviolet ray emission to be hydrophilic andselectively emitting ultraviolet rays to a region in which thebiological substance S is desired to be held. In addition, for example,when the holding surface 111 is treated with avidin, the biologicalsubstance S such as a nucleic acid whose one end is biotinylated can beheld by an avidin-biotin bond. In addition, according to theconfiguration in which a liquid can be held on the holding surface 111,it is also possible to hold the biological substance S in the liquid.

Since the partition wall 13 is made of a conductor, a voltage can beapplied. For example, if a voltage is applied to the partition wall 13when the biological substance S is held on the holding surface 111, thepartition wall 13 functions as an electrode for attracting the chargedbiological substance S, and pushing it to a desired location such as thecenter of a pixel.

The specific structure of the partition wall 13 is not particularlylimited as long as it is provided between the pixels 11 on the holdingsurface 111. For example, as shown in FIG. 8 , each pixel 11 can becompletely partitioned by the partition wall 13. In this case, forexample, when a positive voltage or a negative voltage is applied to allof the partition walls 13 according to the positive and negative chargeof the biological substance S held on the holding surface 111, thebiological substance S can be attracted to the partition wall 13 orcollected in the center of the pixel. More specifically, for example,when negatively charged DNA is detected, if a negative voltage isapplied to all of the partition walls 13, DNA can be collected in thecenter of the pixel. As a result, it is possible to improve detectionaccuracy.

Here, as shown in the schematic cross-sectional view schematicallyshowing a modified example of the first embodiment of the biologicalsubstance detection chip 1 according to the present technology of FIG. 9, the partition wall 13 can have a configuration in which it is embeddedin the semiconductor substrate 12. When the partition wall 13 isembedded in the semiconductor substrate 12, it is possible to preventlight from leaking between pixels, and it is possible to further improvedetection accuracy.

(2) SECOND EMBODIMENT

FIG. 10 is a schematic plan view schematically showing a secondembodiment of the biological substance detection chip 1 according to thepresent technology as viewed from above. The biological substancedetection chip 1 according to the second embodiment is an example inwhich the partition wall 13 is not present in the vertical direction asviewed from above, and the partition wall 13 is present only in thelateral direction. In this case, for example, when a positive voltage ora negative voltage is alternately applied to the partition wall 13 inthe lateral direction as viewed from above, the orientation of thebiological substance S can be aligned in a desired direction. Morespecifically, for example, when negatively charged DNA is detected, asin the second embodiment shown in FIG. 10 , if a positive voltage or anegative voltage is alternately applied to the partition wall 13 in thelateral direction as viewed from above, the orientation of DNA can bealigned. As a result, it is possible to improve detection accuracy.

Here, for example, as shown in the schematic cross-sectional viewschematically showing a first modified example of the second embodimentof the biological substance detection chip 1 according to the presenttechnology of FIG. 11 , in order to divide a voltage, a partition wall13 a in the vertical direction as viewed from above can be provided witha space between it and a partition wall 13 b in the lateral direction asviewed from above. In this case, for example, as shown in the schematiccross-sectional view schematically showing a second modified example ofthe second embodiment of the biological substance detection chip 1according to the present technology of FIG. 12 , an insulator 14 may beprovided between the partition wall 13 a in the vertical direction asviewed from above and the partition wall 13 b in the lateral directionas viewed from above. In addition, for example, as shown in theschematic cross-sectional view schematically showing a third modifiedexample of the second embodiment of the biological substance detectionchip 1 according to the present technology of FIG. 13 , a partition wallmade of the insulator 14 can be provided in the vertical direction asviewed from above.

An insulating material that can be used for the biological substancedetection chip 1 can be used as the insulator 14 as long as the effectsof the present technology are not impaired. For example, an oxide filmof silicon oxide (SiO₂) or the like, and a nitride film of siliconnitride (Si₃N₄), silicon oxynitride (SiON) or the like can be used.

(3) THIRD EMBODIMENT

FIG. 14 is a schematic plan view schematically showing a thirdembodiment of the biological substance detection chip 1 according to thepresent technology as viewed from above. The biological substancedetection chip 1 according to the third embodiment is an example inwhich the partition wall 13 is not present in the vertical direction asviewed from above, and the partition wall 13 is present only in thelateral direction. In addition, this is an example in which a 0 Vpartition wall 13 b 3 is arranged between a partition wall 13 b 1 towhich a positive voltage is applied and a partition wall 13 b 2 to whicha negative voltage is applied. When the 0 V partition wall 13 b 3 isarranged, it is possible to stabilize the charge and form a flow of thebiological substance S. More specifically, for example, when negativelycharged DNA is detected, as in the third embodiment shown in FIG. 14 ,when the partition wall 13 b 2 to which a negative voltage is applied,the 0 V partition wall 13 b 3, and the partition wall 13 b 1 to which apositive voltage is applied are arranged in that order, DNA can flowfrom the − side to the + side. For example, DNA can be separated becausethe flow may differ depending on the difference in the charge of DNA. Asa result, detection accuracy can be improved and additional informationcan be obtained.

Here, as in the second embodiment, for example, as shown in theschematic cross-sectional view schematically showing a first modifiedexample of the third embodiment of the biological substance detectionchip 1 according to the present technology of FIG. 15 , in order todivide a voltage, the partition wall 13 a in the vertical direction asviewed from above can be provided with a space between it and thepartition walls 13 b 1 to 3 in the lateral direction as viewed fromabove. In this case, for example, as shown in the schematiccross-sectional view schematically showing a second modified example ofthe third embodiment of the biological substance detection chip 1according to the present technology of FIG. 16 , the insulator 14 may beprovided between the partition wall 13 a in the vertical direction asviewed from above and the partition walls 13 b 1 to 3 in the lateraldirection as viewed from above. In addition, for example, as shown inthe schematic cross-sectional view schematically showing a thirdmodified example of the third embodiment of the biological substancedetection chip 1 according to the present technology of FIG. 17 , apartition wall made of the insulator 14 can be provided in the verticaldirection as viewed from above.

(4) FOURTH EMBODIMENT

FIG. 18 is a schematic plan view schematically showing a fourthembodiment of the biological substance detection chip 1 according to thepresent technology as viewed from above. The biological substancedetection chip 1 according to the fourth embodiment is an exampleincluding three regions: a region of the partition wall 13 b 1 to whicha positive voltage is applied, a region of the partition wall 13 b 2 towhich a negative voltage is applied, and a region of the 0 V partitionwall 13 b 3. When the region of the 0 V partition wall 13 b 3 isprovided, it is possible to stabilize the charge and form a flow of thebiological substance S. More specifically, for example, when negativelycharged DNA is detected, as in the fourth embodiment shown in FIG. 18 ,when the partition wall 13 b 2 to which a negative voltage is applied,the 0 V partition wall 13 b 3, and the partition wall 13 b 1 to which apositive voltage is applied are arranged in that order, DNA can flowfrom the − side to the + side. For example, DNA can be separated becausethe flow may differ depending on the difference in the charge of DNA. Asa result, detection accuracy can be improved and additional informationcan be obtained.

FIG. 19 is a schematic plan view schematically showing a modifiedexample of the fourth embodiment of the biological substance detectionchip 1 according to the present technology as viewed from above. As inthis modified example, when the region of the partition walls 13 b 2 and13 b 1 to which a positive voltage or a negative voltage is applied isinserted between the regions of the 0 V partition walls 13 b 3, thebiological substance S can be collected in the center of the biologicalsubstance detection chip 1. More specifically, for example, whennegatively charged DNA is detected, as in the modified example of thefourth embodiment shown in FIG. 19 , if the region of the partition wall13 b 1 to which a positive voltage is applied is inserted between theregions of the 0 V partition walls 13 b 3, DNA can be collected in thecenter of the biological substance detection chip 1.

(5) OTHER EXAMPLES

As other examples, although not shown, for example, the magnitude of thevoltage applied to the partition wall 13 can be adjusted. For example,for each area, when the magnitude of the voltage applied to thepartition wall 13 is adjusted, it is possible to collect a desiredbiological substance S for each area according to the charge of thebiological substance S.

Although not shown, some or all of the partition walls 13 describedabove may be covered with a protective film. When the partition wall 13is covered with a protective film, the thinness of the protective filmand the material of the protective film are selected so that thepartition wall 13 is conductive on the holding surface 111. When theprotective film is provided, weather resistance to heat, light, water,acids, alkalis, chemicals and the like can be improved, and it ispossible to keep the partition wall 13 in contact with water, acid,alkalis, or chemicals for a long time.

The material forming the protective film can be freely selected as longas the effects of the present technology are not impaired. For example,silicon oxide (SiO₂), silicon nitride (Si₃N₄), silicon oxynitride (SiON)and the like can be used.

(6) Method of Applying Voltage

The method of applying a voltage to the partition wall 13 can be freelydesigned as long as the effects of the present technology are notimpaired. For example, as shown in the end view taken along the lineB-B, schematically showing the first embodiment of the biologicalsubstance detection chip 1 according to the present technology shown inFIG. 20 , in the invalid pixel region O, a voltage can be applied byconnecting the partition wall 13 to a gate 15 via the semiconductorsubstrate 12. In this case, the gate 15 can control the positive chargeor the negative charge. In addition, although not shown, in thepartition wall 13 of the invalid pixel region O, it is possible to applyan external voltage from the upper side of the chip.

The method in which the partition wall 13 has 0 V can be freely designedas long as the effects of the present technology are not impaired. Forexample, as shown in the schematic end view taken along the line C-C,schematically showing the third embodiment of the biological substancedetection chip 1 according to the present technology shown in FIG. 21 ,0 V can also be obtained by connecting the partition wall 13 b 3 to aP-type region 113.

3. Biological Substance Detection Device 2

FIG. 22 is a block diagram showing a concept of the biological substancedetection device 2 according to the present technology. The biologicalsubstance detection device 2 according to the present technologyincludes at least the above biological substance detection chip 1according to the present technology and an analysis unit 21. Inaddition, according to their purpose, a light emission unit 22, astorage unit 23, a display unit 24, a temperature control unit 25 andthe like can be provided. Hereinafter, respective units will bedescribed. Here, since the biological substance detection chip 1 is asdescribed above, descriptions thereof will be omitted here.

(1) Analysis Unit 21

In the analysis unit 21, optical information acquired by the biologicalsubstance detection chip 1 is analyzed. For example, based on theoptical information acquired by the biological substance detection chip1, checking whether the biological substance S is present, checkingwhether there is an interaction with the biological substance S, andscreening of medicinal components and the like are performed.

Here, the analysis unit 21 may be implemented in a personal computer ora CPU, or may be stored as a program in a hardware resource including arecording medium (for example, a nonvolatile memory (a USB memory), anHDD, or a CD) and the like, and can function by a personal computer or aCPU.

(2) Light Emission Unit 22

The biological substance detection device 2 according to the presenttechnology can include, for example, the light emission unit 22 foremitting excitation light. The light emission unit 22 emits light to thebiological substance S held on the holding surface 111 of the biologicalsubstance detection chip 1. Here, in the biological substance detectiondevice 2 according to the present technology, the light emission unit 22is not essential, and light can be emitted to the biological substance Susing an external light emission device or the like.

The type of light emitted from the light emission unit 22 is notparticularly limited, but in order to reliably generate fluorescence orscattered light from microparticles, light having a constant lightdirection, wavelength, and light intensity is desirable. As an example,a laser, an LED and the like may be exemplified. When a laser is used,the type thereof is not particularly limited, and an argon ion (Ar)laser, a helium-neon (He—Ne) laser, a dye laser, a krypton (Cr) laser, asemiconductor laser, and a solid laser in which a semiconductor laserand a wavelength conversion optical element are combined can be usedalone or two or more thereof can be freely used in combination.

According to their purpose, a plurality of light emission units 22 maybe provided. For example, one light emission unit 22 may be provided foreach pixel 11 of the biological substance detection chip 1. In addition,when a substrate in which light emitting elements such as LEDs arearranged at positions corresponding to the pixels 11 of the biologicalsubstance detection chip 1 is laminated on the biological substancedetection chip 1, light can be emitted to the biological substance S.

(3) Storage Unit 23

The biological substance detection device 2 according to the presenttechnology can include the storage unit 23 in which various types ofinformation are stored. The storage unit 23 can store all items relatedto detection such as optical data acquired by the biological substancedetection chip 1, analysis data generated by the analysis unit 21, andoptical data emitted by the light emission unit 22.

In the biological substance detection device 2 according to the presenttechnology, the storage unit 23 is not essential, and an externalstorage device may be connected. As the storage unit 23, for example, ahard disk or the like can be used.

(4) Display Unit 24

The biological substance detection device 2 according to the presenttechnology can include the display unit 24 that displays various typesof information. The display unit 24 can display all items related todetection such as optical data acquired by the biological substancedetection chip 1, analysis data generated by the analysis unit 21,optical data emitted by the light emission unit 22, data stored in thestorage unit 23 and the like.

In the biological substance detection device 2 according to the presenttechnology, the display unit 24 is not essential, and an externaldisplay device may be connected. As the display unit 24, for example, adisplay, a printer or the like can be used.

(5) Temperature Control Unit 25

The biological substance detection device 2 according to the presenttechnology can include the temperature control unit 25 that keeps thebiological substance S held on the holding surface 111 of the biologicalsubstance detection chip 1 at a predetermined temperature and heats orcools it to a predetermined temperature. For example, when thebiological substance S is an enzyme, the temperature control unit 25 cancontrol the temperature so that an optimal temperature is maintained. Inaddition, when the biological substance S is a nucleic acid, and thepresence of hybridization is detected using the present technology, thetemperature control unit 25 can perform control so that the temperaturerange in which hybridization is possible is maintained. As thetemperature control unit 25, a thermoelectric element such as a Peltierelement can be used.

According to their purpose, a plurality of temperature control units 25may be provided. For example, one temperature control unit 25 may beprovided for each pixel 11 of the biological substance detection chip 1.In addition, when a substrate in which thermoelectric elements arearranged at positions corresponding to the pixels 11 of the biologicalsubstance detection chip 1 is laminated on the biological substancedetection chip 1, the temperature of the biological substance S can becontrolled.

Here, in the biological substance detection device 2 according to thepresent technology, the temperature control unit 25 is not essential,and the temperature of the biological substance S can be controlledusing an external temperature control device or the like.

4. Biological Substance Detection System 3

FIG. 27 is a block diagram showing a concept of the biological substancedetection system 3 according to the present technology. The biologicalsubstance detection system 3 according to the present technologyincludes at least the above biological substance detection chip 1according to the present technology and an analysis device 31. Inaddition, according to their purpose, a light emission device 32, astorage device 33, a display device 34, a temperature control device 35and the like can be provided.

The biological substance detection chip 1 and respective devices can beconnected via a wired or wireless network. Here, since details ofrespective devices are the same as details of respective units of thebiological substance detection device 2 of the present technologydescribed above, descriptions thereof will be omitted here.

Here, in the present technology, the following configurations can beused.

(1) A biological substance detection chip which is composed of aplurality of pixels in which the pixel at least includes a holdingsurface on which a biological substance is held and a photoelectricconversion unit that is provided below the holding surface and providedon a semiconductor substrate, wherein a partition wall made of aconductor is provided between the pixels on the holding surface.

(2) The biological substance detection chip according to (1), wherein avoltage is applied to the partition wall when the biological substanceis detected.

(3) The biological substance detection chip according to (2), wherein apositive voltage or a negative voltage is applied to all of thepartition walls.

(4) The biological substance detection chip according to (2), wherein apositive voltage or a negative voltage is applied to the partition wall.

(5) The biological substance detection chip according to any one of (2)to (4), wherein a magnitude of a voltage applied to the partition wallis able to be changed for each partition wall.

(6) The biological substance detection chip according to any one of (1)to (5), wherein some or all of the partition walls that are able to beconductive on the holding surface are covered with a protective film.

(7) The biological substance detection chip according to any one of (1)to (6), wherein the biological substance is one or more biologicalsubstances selected from among nucleic acids, proteins, cells,microorganisms, chromosomes, ribosomes, mitochondria, organelles (cellorganelles), and complexes thereof.

(8) A biological substance detection device, including; a biologicalsubstance detection chip which is composed of a plurality of pixels inwhich the pixel includes at least a holding surface on which abiological substance is held and a photoelectric conversion unit that isprovided below the holding surface, and in which a partition wall madeof a conductor is provided between the pixels on the holding surface;and an analysis unit that analyzes electrical information acquired bythe biological substance detection chip.

(9) A biological substance detection system, including; a biologicalsubstance detection chip which is composed of a plurality of pixels inwhich the pixel includes at least a holding surface on which abiological substance is held and a photoelectric conversion unit that isprovided below the holding surface, and in which a partition wall madeof a conductor is provided between the pixels on the holding surface;and an analysis device that analyzes electrical information acquired bythe biological substance detection chip.

REFERENCE SIGNS LIST

1 Biological substance detection chip

11 Pixel

S Biological substance111 Holding surface12 Semiconductor substrate112 Photoelectric conversion unit13 Partition wall

14 Insulator 15 Gate

113 P-type region21 Analysis unit22 Light emission unit23 Storage unit24 Display unit25 Temperature control unit31 Analysis device32 Light emission device33 Storage device34 Display device35 Temperature control device

1. A biological substance detection chip which is composed of aplurality of pixels in which the pixel at least includes a holdingsurface on which a biological substance is held and a photoelectricconversion unit that is provided below the holding surface and providedon a semiconductor substrate, wherein a partition wall made of aconductor is provided between the pixels on the holding surface.
 2. Thebiological substance detection chip according to claim 1, wherein avoltage is applied to the partition wall when the biological substanceis detected.
 3. The biological substance detection chip according toclaim 2, wherein a positive voltage or a negative voltage is applied toall of the partition walls.
 4. The biological substance detection chipaccording to claim 2, wherein a positive voltage or a negative voltageis applied to the partition wall.
 5. The biological substance detectionchip according to claim 2, wherein a magnitude of a voltage applied tothe partition wall is able to be changed for each partition wall.
 6. Thebiological substance detection chip according to claim 1, wherein someor all of the partition walls that are able to be conductive on theholding surface are covered with a protective film.
 7. The biologicalsubstance detection chip according to claim 1, wherein the biologicalsubstance is one or more biological substances selected from amongnucleic acids, proteins, cells, microorganisms, chromosomes, ribosomes,mitochondria, organelles (cell organelles), and complexes thereof.
 8. Abiological substance detection device, comprising: a biologicalsubstance detection chip which is composed of a plurality of pixels inwhich the pixel includes at least a holding surface on which abiological substance is held and a photoelectric conversion unit that isprovided below the holding surface, and in which a partition wall madeof a conductor is provided between the pixels on the holding surface;and an analysis unit that analyzes electrical information acquired bythe biological substance detection chip.
 9. A biological substancedetection system, comprising: a biological substance detection chipwhich is composed of a plurality of pixels in which the pixel includesat least a holding surface on which a biological substance is held and aphotoelectric conversion unit that is provided below the holdingsurface, and in which a partition wall made of a conductor is providedbetween the pixels on the holding surface; and an analysis device thatanalyzes electrical information acquired by the biological substancedetection chip.